rs4466467

Variant names:

• chr9-123399942-G-A
• rs4466467
• NM_001352964.2:c.1631+3460C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-123399942-G-A
• chr9-123399942-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352964.2(DENND1A):​c.1631+3460C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0946 in 152,246 control chromosomes in the GnomAD database, including 735 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.095 (735 hom., cov: 32)
• Consequence: DENND1A NM_001352964.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• Publications: 10 publications found

Genes affected

DENND1A (HGNC:29324): (DENN domain containing 1A) Clathrin (see MIM 118955)-mediated endocytosis is a major mechanism for internalization of proteins and lipids. Members of the connecdenn family, such as DENND1A, function as guanine nucleotide exchange factors (GEFs) for the early endosomal small GTPase RAB35 (MIM 604199) and bind to clathrin and clathrin adaptor protein-2 (AP2; see MIM 601024). Thus, connecdenns link RAB35 activation with the clathrin machinery (Marat and McPherson, 2010 [PubMed 20154091]).[supplied by OMIM, Nov 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DENND1A	NM_001352964.2	c.1631+3460C>T		intron_variant	Intron 21 of 23	ENST00000394215.7	NP_001339893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DENND1A	ENST00000394215.7	c.1631+3460C>T		intron_variant	Intron 21 of 23	5	NM_001352964.2	ENSP00000377763.4
DENND1A	ENST00000473039.5	n.1440+3460C>T		intron_variant	Intron 15 of 17	1
DENND1A	ENST00000373624.6	c.1577+3460C>T		intron_variant	Intron 20 of 21	5		ENSP00000362727.2
DENND1A	ENST00000373620.7	c.*1868C>T		downstream_gene_variant		1		ENSP00000362722.3

Frequencies

GnomAD3 genomes AF: 0.0946 AC: 14390 AN: 152128 Hom.: 732 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0383

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0757

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0749

Gnomad OTH AF: 0.100

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0946 AC: 14407 AN: 152246 Hom.: 735 Cov.: 32 AF XY: 0.0948 AC XY: 7057 AN XY: 74434

African (AFR) AF: 0.125 AC: 5188 AN: 41540

American (AMR) AF: 0.114 AC: 1742 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 538 AN: 3472

East Asian (EAS) AF: 0.0382 AC: 198 AN: 5186

South Asian (SAS) AF: 0.105 AC: 508 AN: 4824

European-Finnish (FIN) AF: 0.0757 AC: 803 AN: 10608

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.0749 AC: 5095 AN: 68004

Other (OTH) AF: 0.0992 AC: 210 AN: 2116

Alfa AF: 0.0874 Hom.: 1080

Bravo AF: 0.0998

Asia WGS AF: 0.0670 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.68
PhyloP100		0.040
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4466467; hg19: chr9-126162221;